tbuckley/cabot-search huggingface dataset:
Measuring real-world concordance with evidence-based guidelines for genetic testing in patients with breast cancer: A retrospective quality review.
Authors: Charlotte Ezratty, Alaina J. Kessler, Paula Klein
Journal: Journal of Clinical Oncology (2023)

e22542 Background: Genetic testing plays an important role in the detection and management of breast cancer. Patients with high-risk mutations may undergo more frequent screening and possible risk reduction with medical and surgical management. Genetic testing also guides treatment decisions, including the recent approval of adjuvant olaparib for patients with high-risk BRCA1/2-mutated early-stage breast cancer. The most recent NCCN guidelines expand the age recommendation for genetic testing for patients with a personal history of breast cancer from age ≤ 45 years to ≤ 50 years though in clinical practice, it is likely patients age 46-50 were undergoing genetic testing prior to this recommendation. The goal of this quality review was to assess real-world concordance with genetic testing as per NCCN guidelines and evaluate practice patterns of genetic testing in patients age 46-50 at two large academic centers with a diverse patient population. Methods: We conducted a retrospective quality review of patients age ≤ 50 years diagnosed with early-stage breast cancer at two academic centers from 2019 to 2021. Imaging, pathology, and genetic testing were abstracted from medical records. Baseline characteristics included age, gender, race, ethnicity, stage at diagnosis, receptor status, and genetic testing data. We used descriptive statistics to describe the population and genetic testing results. Results: There were a total of 376 patients with an average age of 44 years. Of these patients, 374 (99%) were female, 158 (42%) white, 76 (20%) African American, 60 (16%) Asian, and 77 (20%) identified as Hispanic. There were 255 patients (68%) diagnosed with stage I cancer, 82 (22%) with stage II, and 39 (10%) with stage III. There were 261 patients (69%) with hormone-receptor positive, HER2-negative cancer and 45 patients (12%) with triple-negative breast cancer (TNBC). Of the 230 patients age ≤ 45, 225 (98%) completed genetic testing. Of the patients who did not undergo genetic testing, 2 were offered and declined. Genetic mutations were found in 25 patients including 13 patients with BRCA1 and 4 patients with BRCA2. Of the 146 patients age 46-50, 134 (92%) completed genetic testing. Excluding patients with TNBC as genetic testing is recommended at any age for patients with TNBC, 115 patients (91%) underwent genetic testing. Mutations were identified in 8 patients including 3 patients with BRCA1 and 2 patients with BRCA2. Conclusions: Genetic testing is a key component of the pre-treatment diagnostic evaluation for patients with breast cancer given implications for management. Our study demonstrated nearly all patients age ≤ 45 with early-stage breast cancer underwent genetic testing, reflecting concordance with evidence-based guidelines. Furthermore, most patients age 46-50 at our institution had undergone genetic testing prior to the expanded NCCN guidelines.
Real-world treatment patterns of triple-class refractory (TCR) multiple myeloma (MM) across the United States (US), Canada, and western Europe: A retrospective chart study.
Authors: Xavier Guillaume, Dahbia Horchi, Jorge Gomez, Patrick Hlavacek, Jinma Ren, Alex Schepart, Didem Aydin, Marco DiBonaventura
Journal: Journal of Clinical Oncology (2023)

e18826 Background: Many patients with MM relapse or become refractory to various therapeutic approaches and typically cycle through many lines of treatment. The present study sought to understand how patients with TCR MM (ie, refractory to ≥1 PI, ≥1 IMiD, and ≥1 anti-CD38 therapy) are managed across various countries. Methods: A non-interventional, retrospective chart review study was conducted across the US, Canada (CA), the UK, France (FR), Germany (DE), Italy (IT), and Spain (ES). Oncologists/hematologists were recruited to abstract medical chart information into an electronic case report form from eligible MM patients (eg, refractory to ≥1 IMiD, ≥1 PI, and ≥1 anti-CD38 antibody treatment, ECOG≤2, and initiated their first therapy after their TCR status [ie, their index therapy] between 1/1/2018 and 12/31/2020 to ensure at least 1 year of follow-up). Abstractions were performed from January through April 2022. Demographics, clinical characteristics, and treatment patterns were descriptively analyzed and reported here. Results: N = 314 patients with TCR MM were included (56.7% male; median age = 70). Clinical characteristics were similar to other TCR MM studies (eg, 26.1% had an ECOG score of 2, 25.8% had high cytogenetic risk (ie, t(4:14), t(14:16), and/or del(17p), and 10.2% had extramedullary disease). Patients received a median of 3 treatment lines prior to their index therapy, with 70 unique treatment regimens reported as part of their index therapy line (Table 1). The most common regimens (&gt; 10%) were Pd and Kd. Conclusions: This global chart review across the US, Canada, and Western Europe highlights the consistent lack of a standard of care for the management of MM among patients who are refractory to the three main classes of therapies. [Table: see text]
Cerebrospinal fluid circulating tumor DNA for the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.
Authors: Qian Miao, Xinlong Zheng, Xiaobin Zheng, Kan Jiang, Gen Lin, Longfeng Zhang
Journal: Journal of Clinical Oncology (2023)

e21039 Background: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. Methods: Patients with LM from NSCLC were retrospectively analyzed. Circulating tumor DNA (ctDNA) of CSFand pairedextracranial tissue or plasma were tested by ARMS or next-generation sequencing(NGS).Clinical outcomes were compared with Kaplan-Meier log-rank test and Coxproportional hazards methodologies. Results: We reviewed charts of 80 patients with LM treated atFujian Cancer Hospital. A total of 57 CSF and of which 30 contemporaneouslypaired extracranial samples tested by NGS were analyzed. Most interestingly, CSF ctDNA revealed EGFR mutations in 4 patients previously diagnosed as wild-type by extracranial specimens, and survival was extended by targeted therapy. In the gene map of paired samples, CSF showed more abundant cell-cycle regulatory genes and complex independent evolutionary. CDKN2A/2B CNVs-del was enriched threefold in CSF (~26.3%) with LM compared to extracranial specimens (~8.9%)in lung adenocarcinoma without LM. The median overall survival (OS) was 14.1 months [95% confidence interval (CI): 10.7–17.5 months]. Univariate analyses and multivariate Cox analyses demonstrated that patients with CDKN2A/CDKN2Bco-mutation had poor prognosis. Conclusions: CSF-based ctDNA testing contributes to the phenotypic detection and unique characterization of resistance mechanisms of LM in NSCLC. CDKN2A/2B mutation maybe a poor prognostic factor in LM patients.
Correlation analysis of MRD positivity after non-small cell lung cancer surgery.
Authors: Daling Dong, Bin Jiang, Wei Wei, Chao Wang, Qian Yang, Tingzhi Yan, Liken Zheng, Weikang Shao, Gang Xiong, Shixin Zhang
Journal: Journal of Clinical Oncology (2023)

e20590 Background: To explore the relationship between postoperative molecular residual disease (MRD) status in patients with non-small cell lung cancer (NSCLC) and clinicopathological features, gene mutations, the tumour immune microenvironment and treatment effects. Methods: The clinical data of 90 patients with stage I-IIIA NSCLC who underwent radical resection of lung cancer from January 2021 to March 2022 in our hospital were retrospectively collected, and demographic data, clinicopathological characteristics, genetic test results, MRD status, and treatment effects were analysed. Results: Sex, age, smoking status, pathological type, and gene mutations were not associated with postoperative MRD status. T (tumour diameter &gt; 3 cm) and N (lymph node metastasis) were statistically correlated with MRD positivity ( p values of 0.004 and 0.003, respectively). The higher the proportion of micropapillary and solid pathological subtypes of lung adenocarcinoma, the higher was the MRD-positivity rate after surgery ( p = 0.005). MRD positivity was correlated with vascular invasion ( p = 0.0002). For the expression of programmed cell death ligand 1 (PD-L1), tumour positive score (TPS) ≥ 1% and combined positive score (CPS) ≥ 5 were correlated with postoperative MRD status ( p value distribution was 0.0391 and 0.0153). For ctDNA clearance, among postoperative MRD-positive patients, postoperative adjuvant targeted therapy was superior to chemotherapy for patients without gene mutations. Conclusions: Postoperative ctDNA-MRD status in NSCLC patients is associated with primary tumour size, lymph node metastasis, lung adenocarcinoma pathological subtype, vascular invasion, TPS and CPS for PD-L1 expression; for postoperative MRD-positive patients, clearance of ctDNA by adjuvant EGFR-TKI target treatment is superior to chemotherapy.
A differential analysis of TCR repertoire between patients with EGFR-mutant and KRAS-mutant non–small-cell lung cancer.
Authors: Yuancai Xie, Yingmei Li, Linfeng Dong, Shifu Chen, Jixian Liu
Journal: Journal of Clinical Oncology (2023)

e21012 Background: T-cell receptor (TCR) repertoire could partially represent tumor micro-environment. EGFR and KRAS are common driver genes mutated and often mutually exclusive in non-small cell lung cancer (NSCLC). There’s a hypothesis that the immune system responds differently according to different mutations. Here we investigated the TCR features, including diversity, clonality, evenness and sequence similarity in EGFR and KRAS mutated NSCLC patients, to better understand the immune response in carcinogenesis. Methods: A total of 71 EGFR-mutant and 31 KRAS-mutant NSCLC tissue samples underwent multiplex PCR based TCR-β sequencing. TCR-β cdr3 amino acid sequences were obtained from the sequencing data using MiXCR and VDJtools. To compare TCR repertoires in EGFR-mutant and KRAS-mutant groups, each assemble CDR3 amino acid sequence was taken as a word, and each repertoire was taken as a document. Each repertoire was compared with every other one as a sample pair. TF-IDF (term frequency-inverse document frequency) document vectors was built for each sample and cosine similarity scores were computed for sample pairs. Results: The total cosine similarity score within EGFR-mutant group is 11.07 and average cosine similarity score is 0.0044±0.01, while in the KRAS-group, the total cosine similarity score is 13.41 and average cosine similarity score is 0.029±0.04. Between these two groups, the total cosine similarity score is 8.76 and average cosine similarity score is 0.0019±0.0009. See table for summary. The intergroup similarity score is significantly less than that within each group respectively (p &lt; 1E10). Conclusions: Our results demonstrated that the TCR repertoire was clearly associated with cancer mutational profile. The mechanism of how mutations affect the immune system and shape the TCR repertoire is yet to be investigated. [Table: see text]
Novel curriculum for training in medical cannabis in oncologic populations for oncology trainees.
Authors: Rushad Patell, Poorva Bindal, Laura E. Dodge, Gayathri Nagaraj, Ann S. LaCasce, Mary K. Buss, Mara A. Schonberg, Ilana Monica Braun, Jason Freed, Deepa Rangachari
Journal: Journal of Clinical Oncology (2023)

11013 Background: There is continued uptake in the use of medical cannabis (MC) among patients with cancer. Our group previously conducted a national study that showed that while a majority of oncology fellows discussed MC with patients, very few feel well informed in doing so. We hypothesized that an evidence-based curriculum on the use of MC for oncology trainees is feasible to develop and would be effective in improving confidence to discuss MC with patients. Methods: A multidisciplinary expert team designed an evidence-based educational curriculum in 5 modules specifically for MC in oncology populations that included pharmacology/history, symptom management, cancer-directed effects, toxicities and practical/logistic concerns. The curriculum was piloted as a one-hour webinar at three US hematology oncology fellowship training programs in 2022-2023. Anonymous incentivized survey instruments that were designed to assess self-perceived knowledge, attitudes and behaviors pertaining to MC (on a 5-point Likert scale; strongly agree to strongly disagree) were distributed anonymously via email at the pilot (t = 0) and immediately after (t + 7 days); additional delayed surveys (t+90 days) are in progress. Results: Of 35 eligible trainees, 31 completed the pre-training surveys (88.6%), and 26 (74.3%) completed the post-training surveys. Most trainees indicated that the curriculum is helpful (88.5%, 95% CI: 69.8-97.6) and that they would recommend it to their colleagues (80.8%, 95% CI: 60.6-93.4). Following the webinar, there was significant improvement in self-reported comfort with discussing MC for symptom management (3.2% vs. 92.3%, P &lt; 0.001), risks of MC (9.7% vs. 76.9%, P &lt; 0.001) and modes of MC use (16.1 vs. 80.8%, P &lt; 0.001). The majority of participants (80.0%, 95% CI: 59.3-93.2) reported that they were more likely to initiate conversations about MC with their patients after attending the webinar. Conclusions: In this multi-center study, we demonstrate that it is feasible to develop and deliver a fellow-focused, evidence-based curriculum for MC use in patients with cancer. The webinar was well received and demonstrated significant improvement in fellow-reported attitudes surrounding MC efficacy, risks, and modes of use. Further work to assess durability of the curriculum on knowledge, attitudes, and behaviors is ongoing.
Prevalence of actionable oncogenic alterations (AGA) among patients with advanced (adv) non-squamous (NSQ) non-small cell lung cancer (NSCLC) by age, sex, and race in the United States (US).
Authors: Sabine Oskar, Ke (Kirsten) Zu, Ashwini Arunachalam, Yu-Han Kao, Cai Chen, Bin Zhao, Himani Aggarwal
Journal: Journal of Clinical Oncology (2023)

e21206 Background: Identification of AGA in NSCLC has improved the understanding of lung cancer pathogenesis and introduced targeted therapies directed against specific genomic alterations. Given the limited data on the prevalence of AGA by demographics, we evaluated prevalence of AGA by age at diagnosis (dx), sex, and race. Methods: A descriptive study used the US nationwide de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database. Eligible patients were adults with a dx of adv NSQ NSCLC from Jan-2016 to Sep-2020 who initiated a first line therapy. The prevalence of AGA for each age, sex, or race stratum was calculated. Results: The cohort included 3938 patients; 67.9% White, 52.9% female, and median age at dx was 68 y. Table 1 presents the prevalence of AGA. The prevalence of EGFR and BRAF V600E mutations increased with age at dx. ALK rearrangement and ROS1 fusion were more prevalent among patients &lt; 50 y vs ≥50 y while MET exon 14 skipping mutation was more prevalent among patients ≥75 y vs &lt; 75 y. EGFR and KRAS G12C mutations were more prevalent in female vs male. Compared to White or Black, Asians had a higher prevalence of EGFR mutations and lower prevalence of KRAS G12C. Conclusions: The prevalence of certain AGA among patients with adv NSCLC vary by demographics, which may contribute to disproportionate disease burden in certain strata. These results highlight the need to enhance diversity of clinical trial populations and ensure the disease burden across demographics in the general population are represented in clinical trials. [Table: see text]
Does the landscape of comprehensive genomic profiling in patients with advanced stage lung cancer in India differ from data from the western countries.
Authors: Ankur Bahl, Niti Raizada, Aparna Dhar, Amit Agarwal, Rajat Bajaj, Nitesh Rohatgi
Journal: Journal of Clinical Oncology (2023)

e21011 Background: Lung cancer is one of the leading causes of cancer related deaths worldwide and India. The understanding of the molecular basis of lung cancer has led to increased number of FDA approved targeted therapies and therefore survival. Data on the molecular landscape of lung cancers has a preponderance of western and east Asia. India while may harbour one third of world new lung cancer case, the understanding of comprehensive molecular landscape of lung cancer in India is poor. Methods: We have retrospectively compared comprehensive genomic profiling of lung cancer patients across three centres over a period of two years using foundation one cdx. We aim to compare this to available data from rest of the world and present the differences and commonalities. We believe this will help understand both differences in presentations and pattern of disease as well as question if treatment algorithms should be same or different. At least on this occasion we will limit our study to foundation one CDx patients only so that comparison with western data is not confounded by differences in technology. Results: We have Highlighted 44 such patients and will be comparing their data to the available data on foundation on CDX from available literature. 27 (61.3%) patients had one of the most common targetable mutations including EGFR ALK ROS MET BRAF ERBB2 and NTRK. Surprisingly 9(20.4%) had mutations in the homologus repair pathway. 3 patients also had MSI High. We will present comparison of this Indian data to that's available across the world. Conclusions: Precision Oncology and molecular biology is cornerstone of cancer care especially in Lung Cancer. We want to deepen the understanding of the comparison of Indian cohort and believe its different with arguably more targetable abnormalities detected than in the west and similar to the eastern population of the world.
Towards organ preservation and cure via 2 infusions of immunotherapy only, in patients normally undergoing extensive and mutilating curative surgery for cutaneous squamous cell carcinoma: An investigator-initiated randomized phase II trial—The MATISSE trial.
Authors: Charlotte L. Zuur, Sabine Breukers, Mercedes Machuca-Ostos, Thomas Boere, Laura Smit, J.P. De Boer, Sten Cornelissen, Arash Navran, Winan J. van Houdt, Bram Westerink, Maurits Wondergem, Remco de Bree, Lot A. Devriese, Daniela Thommen, Joleen Traets, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2023)

9507 Background: Standard of care for locally advanced cutaneous SCC (CSCC) consists of extensive and mutilating surgery often with adjuvant radiotherapy (RT). To improve clinical prospects of these patients (pts), we tested efficacy of neoadjuvant nivolumab (NIVO) and nivolumab plus ipilimumab (COMBO) in pts with CSCC with an indication for extensive surgery with or without adjuvant RT. Methods: 40 pts with T1-4N0-3M0 or TxN1-3M0 CSCC and an indication for extensive and/or mutilating surgery were needed to reach the primary objective of this trial. Pts were randomized for ARM A: NIVO (3 mg/kg, weeks 0&amp;2, N = 26) or ARM B: NIVO (3 mg/kg, weeks 0&amp;2) + IPI (1mg/kg, week 0, N = 24) prior to surgery (week 4). Primary objective was pathological response at time of surgery. A major pathological response (MPR) was defined as ≤10% residual viable cancer cells in the surgical resection specimen. Secondary endpoints were tolerability (CTCAE v.5.0), survival, and quality of life (QOL). Key exploratory aim for the trial was the serial collection of pre- and on-treatment tumor samples to investigate immunogenomic features correlating with immunotherapy response. Preliminary results: 50 pts were enrolled at median age 76, of whom 32% with TxN1-3M0 disease. Grade 3-4 irAEs occurred in 6 (12%) pts and were well manageable. 40 pts underwent standard of care surgery w/wo adjuvant RT, of whom 40% and 53% reached an MPR upon NIVO and COMBO, respectively. However, 10 pts withdrew consent to undergo surgery and RT, of whom nine pts declined because of self-reported substantial clinical remission upon neoadjuvant immunotherapy. These clinical responses were confirmed via FDG-PET evaluation in week 4. All these 9 pts are currently cancer free at median FU of 12 months (range 4 to 27) with superior QOL compared to MATISSE pts undergoing standard of care. Overall, we found deep clinical responses in 13/26 (50%) and 14/23 (61%) of pts upon NIVO and COMBO, respectively, being either a MPR at time of surgery or a clinical CR in patients declining surgery. Preliminary conclusions: The MATISSE trial shows deep responses of 50% and 61% upon neoadjuvant NIVO and COMBO, respectively, with well manageable toxicity in this elderly CSCC population. Nine MATISSE patients have proven the concept that organ preservation and durable complete remissions can be achieved after two infusions of neoadjuvant immunotherapy only, without extensive or mutilating curative surgery and/or RT. Clinical trial information: NCT04620200 .
A flexible quantitative framework to assess the potential contribution of early cancer detection to improved cancer survival.
Authors: Menggang Yu, Christopher Tyson, Paul J. Limburg, Tomasz M. Beer
Journal: Journal of Clinical Oncology (2023)

e22508 Background: Public health goals often articulate aspirations to improve cancer survival by some pre-specified percentage. Such survival improvements may be achieved through a combination of medical interventions and lifestyle change. Early detection of cancer can contribute to cancer survival improvements. Impact of early detection programs is realized both through innovation driving advances in screening technologies and increased access and adherence with screening tests. We develop a quantitative approach to characterize the magnitude of early detection across multiple cancer types that corresponds to a specified percent improvement in survival. Methods: A matrix equation is developed relating survival and stage shift. The percent of survival improvement is defined a priori as 20% in this case but can be set to other percentages. We populate the matrix equation with incidence and cause-specific survival for 15 cancers by stage at diagnosis from the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. We then use linear programming to solve the matrix for all specified cancers simultaneously given a set of constraints formulated to steer the solution towards the least stage shift required to achieve the objective and to partially compensate for length-time bias. Results: Based on our target survival improvement of 20%, three common trends emerged across 14 of the 15 cancer types: first, we see that the bulk of survival improvement can be achieved by detecting most disease prior to stage 4; second, that the remaining survival improvement can be achieved by detecting most cancers just one stage earlier; and third, that stage 1 diagnosis is generally not necessary to achieve reasonable survival improvement goals. The solution revealed lung cancer as the one type that required more aggressive earlier detection than others, an expected result given that lung cancer has both very high incidence and very poor survival. Conclusions: The mathematical framework we develop is very flexible and can be helpful for public health officials and innovators to characterize the contribution that earlier cancer detection can make towards improved cancer survival. Our results suggest that detecting cancer prior to the development of distant metastases, even after progression beyond stage 1, has potential for significant public health benefit. This approach may also be extended to assess the impact that emerging treatment landscapes, coupled with early cancer detection, may have on improved cancer survival.